Prenatal pyrethroid exposure, placental gene network modules, and neonatal neurobehavior
Year: 2025
Type: article
Study design: Observational Study
Abstract: Prenatal pesticide exposure may adversely affect child neurodevelopment which may partly arise from impairing the placenta's vital role in fetal development. In a cohort of pregnant farmworkers from Thailand (N = 248), we examined the links between urinary metabolites of pyrethroid pesticides during pregnancy, placental gene expression networks derived from transcriptome sequencing, and newborn neurobehavior assessed using the NICU Network Neurobehavioral Scales (NNNS) at 5 weeks of age. Focusing on the 21 gene network modules in the placenta identified by Weighted Gene Co-expression Network Analysis, our analysis revealed significant associations between metabolites and nine distinct modules, and between thirteen modules and NNNS, with eight modules showing overlap. Notably, stress was negatively associated with the interferon alpha response and Myc target modules, and the interferon alpha response module was correlated positively with attention, and negatively with arousal, and quality of movement. The analysis also highlighted the early and late trimesters as critical periods for the exposures influence on placental function, with pyrethroid metabolites measured early in pregnancy significantly negatively associated with the protein secretion module, and those measured later in pregnancy negatively associated with modules related to oxidative phosphorylation (OXPHOS) and DNA repair. Additionally, the cumulative sum of 3-phenoxybenzoic acid across pregnancy was significantly negatively associated with the OXPHOS module. These findings suggest that prenatal exposure to pyrethroids may influence neonatal neurobehavior through specific placental mechanisms that impact gene expression of metabolic pathways, and these effects may be pregnancy period specific. These results offer valuable insights for future risk assessment and intervention strategies.
Authors: Yewei Wang, Jacqueline Holstein, Karen Hermetz, Amber Burt, Corina Lesseur, Parinya Panuwet, Nancy Fiedler, Tippawan Prapamontol, Panrapee Suttiwan, Pimjuta Nimmapirat, Supattra Sittiwang, Warangkana Naksen, Volha Yakimavets, Dana Boyd Barr, Ke Hao, Jia Chen, Carmen J. Marsit
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,800
Awards: G1359611882, G16378805, G252213851, G3881485945, G4011615584, Big Omics Data Engine 2 Supercomputer, Placental Functional Networks Linking Developmental Pesticide Exposure and Offspring Neurodevelopment, Chemical exposure disruption of the placental circadian clock, COVID and Translational Science supercomputer (CATS), Characterizing the functional genomic atlas of human placenta and unveiling the prenatal programming of early-life development
OpenAlex ID: W4413108073